Evaluation of the effect of estrogen on left ventricular remodeling in the rat model

The aim of the present study was to investigate whether estrogen plays a role in
remodeling of the left ventricle in the hearts of female rats. Four groups of animals
were studied: control group, ovariectomized group, ovariectomized receiving
estrogen treatment for 4 weeks and lastly ovariectomized animals receiving both
estrogen and the protein kinase C inhibitor chelerythrene for 4 weeks.
At the end of the four weeks period, the animals were sacrificed and left ventricular
performance, left ventricular axis, left ventricular weight and heart weight were
measured. The ventricular tissue level of metalloproteinase 9 (MMP-9) and the
expression of collagen type I and angiotensin II type I receptors (AT1) were also
assessed.
Results of this work show that ovariectomy induced a reduction in left ventricular
pressure, an increase in left ventricular axis, left ventricular weight and total heart
weight as compared to sham operated group (P<0.05). The animals also showed an
increased expression of collagen type I, AT1 receptors and increased level of MMP- 9
in ventricular tissue samples. Estrogen supplementation in ovariectomized animals
improved the mechanical performance of the heart as evidenced by significant
increase of left ventricular pressure, heart rate and dp/dt towards normal levels. It
also reduces left ventricular hypertrophy and dilatation as significant reduction of left
ventricular axis, left ventricular weight and heart weight towards control levels were
observed. Furthermore, estrogen reduced the expression of collagen type I & AT1
receptors as well as the level of MMP-9 in ventricular tissues (P<0.05). Treatment of
ovariectomized animals with both estrogen and the protein kinase C inhibitor
chelerythrene (group IV) resulted in partial block of the cardioprotective effect of
estrogen treatment alone (group III).
We conclude that estrogen, possibly through a mechanism that involves protein C
activation, seems to reduce left ventricular hypertrophy and dilatation as well as left
ventricular tissue level of MMP- 9 and expression of collagen type I & AT1 receptors
while maintaining left ventricular pressure and performance. Such results suggest a
positive role of estrogen in cardiac protection in female rats through regulating
certain Key elements involved in the process of ventricular remodeling.